Oral Poliomyelitis Vaccine Research Articles

Congenital malformations of the brain misinterpreted as sequelae of poliomyelitis

Poliomyelitis is an infectious disease of the peripheral motor neurons, which predominantly affects children and causes residual palsies. Because of the oral poliomyelitis vaccination started in Germany in 1960 and 1962 and the following rapid decline of the incidence of this infection, the postpolio syndrome in Germany is adisease of older people. Since 2008, we have offered apoliomyelitis outpatient consultation at the Center of Geriatrics, Protestant Hospital Göttingen-Weende and have treated 33patients. The spectrum of persistent deficits after poliomyelitis ranges from palsy of single extremities to severe disability with (temporary) ventilator dependence. Many patients suffer from scoliosis or shortening of limbs of different degrees, which promotes degenerative diseases of the spinal cord and joints with secondary myelopathy, injury of spinal nerve roots or peripheral nerves or respiratory failure. The postpolio syndrome is characterized by an increase of the functional deficits after decades of compensation. The palsies of 2of the 33patients were not caused by poliomyelitis but by myelomeningocele and schizencephaly, respectively. The motor deficits acquired in childhood enable the majority of the patients to successfully master their lives. Because of the limited compensatory capacities of postpolio patients, even small increases in the severity of the palsy can cause asevere decline of the functional status and an impairment of the ability to live an independent life. In asubstantial proportion of patients with the diagnosis poliomyelitis the symptoms are caused by other diseases.

When are antibody determinations in serum before or after vaccination indicated and when not?

Questions about the usefulness of determining antibody values or titers to demonstrate protection often arise before or after vaccinations in immunization clinics. Such measurements may be useful in exceptional situations, e.g., in immunocompromised patients or those with suspected immunodeficiency, in patients with unknown vaccination status, and in certain defined risk situations (e.g., hepatitisB serology after needlestick injuries or after COVID-19 vaccination in patients with certain forms of immunodeficiency). In contrast, individual serological antibody measurements are neither recommended nor useful after generally recommended vaccinations. This is because either it is known from licensure studies or long-term use that there is asufficiently high individual probability of protection (e.g., > 99% for tetanus) when the recommended vaccination schedules are adhered to or because the vaccination strategy is primarily aimed at indirect protection of the population and not at protection of each individual person. The few individuals who are not sufficiently protected after vaccination (vaccination failures) will still benefit indirectly from the reduced risk of exposure. This has been demonstrated with oral poliomyelitis vaccination in the 1960s, MMR vaccination since the 1970s, and Hib vaccination since the 1990s. This statement of our committee shows the evidence for asensible approach, when and which antibody determinations are helpful and meaningful after or before vaccination and which are not. The statement is based on Germany's Standing Committee on Vaccination (STIKO) recommendations and their administration instructions. We advise not to comply with the wish of some parents for titer determinations in their child that are not medically justified.

Immunogenicity and Safety of Inactivated Sabin-Strain Polio Vaccine “PoliovacSin”: Clinical Trials Phase I and II

Global polio eradication requires both safe and effective vaccines, and safe production processes. Sabin oral poliomyelitis vaccine (OPV) strains can evolve to virulent viruses and result in poliomyelitis outbreaks, and conventional inactivated poliomyelitis vaccine (Salk-IPV) production includes accumulation of large stocks of neurovirulent wild polioviruses. Therefore, IPV based on attenuated OPV strains seems a viable option. To increase the global supply of affordable inactivated vaccine in the still not-polio free world we developed an IPV made from the Sabin strains–PoliovacSin. Clinical trials included participants 18–60 years of age. A phase I single-center, randomized, double-blind placebo-controlled clinical trial included 60 participants, who received one dose of PoliovacSin or Placebo. A phase II multicenter, randomized, double-blind, comparative clinical trial included 200 participants, who received one dose of PoliovacSin or Imovax Polio. All vaccinations were well tolerated, and PoliovacSin had a comparable safety profile to the Placebo or the reference Imovax Polio preparations. A significant increase in neutralizing antibody levels to polioviruses types 1–3 (Sabin and wild) was observed in PoliovacSin and Imovax Polio vaccinated groups. Therefore, clinical trials confirmed good tolerability, low reactogenicity, and high safety profile of the PoliovacSin and its pronounced immunogenic properties. The preparation was approved for clinical trials involving infants.

Oral poliomyelitis vaccine, 1960s

Oral poliomyelitis vaccine, 1960s

Determination of Factors Affecting Bivalent (Type 1 and 3) Stability of Oral Poliomyelitis Vaccine

Determination of Factors Affecting Bivalent (Type 1 and 3) Stability of Oral Poliomyelitis Vaccine

Vaccineassociated paralytic poliomyelitis and acute flaccid paralysis on some territories of Russia during 20 years

Aim: Analysis of the morbidity of vaccine-associated paralytic poliomyelitis and acute flaccid paralysis and the results of virological investigation of the patients on 14 territories of the Russian Federation in 1998-2017. Materials and methods: We investigated nearly 3000 stool samples from paralytic patients and contact persons. Isolation and identification of polioviruses were performed according to WHO recommendations with the help of cell lines RD and L20B. We conducted the sequencing of the genome fragments VP3-VP1, VP1-2A and full sequencing of genome region VP1 of 45 poliovirus strains. Results: From 1998 till 2017 1257 cases of acute flaccid paralysis were registered on 14 territories of Russia, 15 cases of which (1,2%) were classified as vaccine-associated paralytic poliomyelitis. From these patients 9 children were non vaccinated and 6 children received from one to four doses of oral poliomyelitis vaccine. The percentage of the detection of polioviruses from the patients and contact persons in different years was not equal and constituted from 3, 4±0,89% to 9, 5±0,79%. All in all from the patients with acute flaccid paralysis and contact persons we isolated 191 polioviruses, 60 of them belonged to type 1, 55 polioviruses were identified as types 2 and 76 as type 3. Some cases of vaccine-associated paralytic poliomyelitis are described in the article; polioviruses were isolated from all these patients. The sequencing of the genome fragments of 45 poliovirus strains showed that the majority of them had the nucleotide substitutions including neurovirulent substitutions. Conclusion:In order to prevent the risk of the appearance of vaccine-associated paralytic poliomyelitis it is necessary to maintain the high quality of surveillance of poliomyelitis and acute flaccid paralysis, to ensure the 95% coverage of children with poliomyelitis vaccine, to minimize the cases of groundless delays of vaccination according to medical recommendations and parents’ refusals to vaccinate children against poliomyelitis and to respect strictly the National calendar of vaccination.

Statistical Analysis of Results from the Attestation of Biological Standard Samples: Use of the Mann-Whitney Test

An algorithm for assessing the possibility of joining two datasets obtained by different operators for attestation of standard samples of biological medicinal substances (SS BMS) is proposed. These studies tested the uniformity of the results obtained by different operators during attestation of industrial standard samples of the specific activity of an oral poliomyelitis vaccine, i.e., divalent live attenuated types 1 and 3 “BiVak polio” vaccine, using the Mann-Whitney and Z statistics for independent sets run manually using a formula, with subsequent interpretation of the results. Results from calculation of the Mann-Whitney test in Statistica software (version 10) are presented.

Wastewater as an Indicator of Virus Circulation among Population of Dnipropetrovsk Oblast, Ukraine

ObjectiveThe purpose of the study was to confirm the hypothesis of possible intestinal viruses circulation in wastewater in Dnipropetrovsk Oblast, Ukraine.IntroductionThe main reservoir of intestinal viruses in the environment is human feces and contaminated wastewater. Sewage contamination preconditions further contamination of surface water serving as a source of water supply [2,7,8]. High resistance to physical and biological exposures ensures long-term survival of the viruses in water with various type and level of contaminants, especially in sewage. Detection of enteroviruses of a specific serotype in sewage indicates a significant number of people releasing the virus with feces [1,2]. There are two peaks of enteroviruses concentration in sewage: in January-April, and in June-September [8]. Sewage testing for enteroviruses is one of effective methods for their detection and risk assessment [3]. European region, including Ukraine, is recognized as free from of wild polioviruses, and a systematic study of sewage samples is important for identifying the possibilities of their "silent" circulation [6].MethodsWastewater samples from large sewerage collectors, sewage wells of infectious departments, city hospitals and district sewerage networks of Dnipropetrovsk Oblast were tested in 2007-2017 (39-64 samples monthly in the points are determined by the national regulations [7]). Gauze tampons (Moore's method) were used to collect wastewater [8]. In addition, samples were collected from wastewater flow into 1-liter sterile bottle with a sampler. Concentration was carried out using Enterosgel (hydroxyl methyl silicic acid) with high adsorption capacity [7]. The supernatant after all the concentration steps was used for culture on cell cultures RD, HEP-2, L20B [4,7,8].In the presence of cytopathic action in RD cells, culture liquid was inoculated into L20B cells to detect clear cytopathic activity. Culture liquids were investigated to identify enteroviruses in neutralization reaction. In HEP-2, cytopathic effects were observed in the form of clusters of different sizes cells, "grape clusters", which indicated the presence of adenoviruses. Adenoviruses were confirmed by immunochromatographic tests for adenovirus antigens "Cito Test Adeno" Pharmasko, Ukraine).ResultsDuring 10 years, 150 viruses were isolated, 2 of them were a mixture of polioviruses. The frequency of detection of enteroviruses (including polioviruses) and adenoviruses was 2.5% (Tab 1).The isolated strains of enteroviruses, including polioviruses, were sent for confirmation the Public Health Center of the Ministry of Health of Ukraine and Regional WHO polio reference laboratories (Moscow and Helsinki). All polio strains were attributed to the vaccine strain Sabin. Also, the result Coxsackie viruses B typing was confirmed.ConclusionsThe data testify to presence of Picornaviridae (polioviruses, Coxsackie B, non-polio enteroviruses (NPEVs), and Adenoviridae in the wastewater in Dnipropetrovsk Oblast, Ukraine. The typical composition of viruses was not constant. Types 1, 2 polioviruses (Sabin) were occasionally isolated from wastewater. Type 2 polioviruses (Sabin) were isolated only in 2015. In 2009, 2012-2014, 2017, polioviruses did not stand out. Polioviruses isolation is associated with mass immunization of children against polioviruses carried out to maintain polio-free status of the country. In average, 150,000 children are vaccinated annually. Oral poliomyelitis vaccine (OPV) produced in Russia, France, Belgium was used in 2007-2017 (attenuated Sabin strains, 1,2,3 types). From April 2016, Ukraine refused to use trivalent OPV and switched to bivalent vaccine (Sabin strains, types 1 and 2).Sewage testing for polioviruses and their differentiation at WHO National and Regional Centers for Polio Diagnosis ensures a system for monitoring of possible "silent" circulation [6]. Sewage testing using cell cultures is one of the most affordable, effective and reliable methods for controlling the presence of viruses in the environment [4,7,8]. RD and L20B cell lines are useful for poliovirus isolation from sewage [4].In addition to polioviruses, 1,2,3 types Coxsackie viruses B were isolated from wastewater samples. However, starting from 2013, Coxsackie viruses were isolated only in sporadic cases (Cox.vir.B5). In 2007-2011, NPEVs were isolated in some cases. Because polio is on the verge of eradication, more attention should be paid to study of NPEVs [5]. For 10 years, adenoviruses were isolated, which are well preserved in wastewater [1]. The maximum number of adenoviruses was isolated in 2014.

Observation on safety of sequential vaccination schedule of different strain inactivated poliovirus vaccines

Objective: To evaluate the safety of population based sequential vaccination schedule of inactivated poliovirus vaccines prepared with different strains. Methods: This randomized, parallel-group controlled trial was conducted from March, 2017 to May, 2018, in Shanghai. Adverse reaction data of Sabin strain inactivated polio vaccine (sIPV), wild strains inactivated polio vaccines (wIPV) and bivalent types Ⅰ and Ⅲ oral poliomyelitis vaccine (bOPV) were systematically collected through active observation in 1 917 infants in Shanghai after the vaccination at 2, 3, 4 months old. The eligible infants aged 2 months were divided into 4 groups: ①sIPV+sIPV+bOPV group; ②sIPV+wIPV+bOPV group; ③wIPV+sIPV+bOPV group; ④wIPV+wIPV+bOPV group. Results: The incidence of adverse reaction 30 days later after 3 basic dose vaccinations was 16.79% (946/5 633). No serious adverse reaction was reported. Local and systemic reactions were mainly mild. Common local reactions were pain, erythema, cutaneous nodule, etc.; and common systemic reactions were abnormal crying, drowsiness, diarrhea and appetite lost, etc.. The incidence of local reactions 30 days later after 3 basic dose vaccinations was 1.65% (93/5 633), and the incidence rates of grade 1-3 reactions were1.26% (71/5 633), 0.21% (12/5 633) and 0.20% (11/5 633) respectively. The incidence rate of systemic reactions 30 days later after 3 basic vaccinations was 15.14% (853/5 633), and the incidence rates of grade 1-3 reactions were 11.33% (638/5 633), 3.18% (179/5 633) and 0.64% (36/5 633) respectively. There were no significant differences in the rate of grade 3 reaction among different groups (χ(2)=4.17, P=0.24). Conclusions: No severe adverse reactions related to sequential vaccination of different strain inactivated polio vaccines were observed, most of reactions were mild and all of them were cured. It is safe to use sIPV and wIPV simultaneously or alternately for childhood sequential vaccination.

A post-conflict vaccination campaign, Central African Republic

ObjectiveTo rapidly increase childhood immunization through a preventive, multi-antigen, vaccination campaign in Mambéré-Kadéï prefecture, Central African Republic, where a conflict from 2012 to 2015 reduced vaccination coverage.MethodsThe three-round campaign took place between December 2015 and June 2016 using: (i) oral poliomyelitis vaccine (OPV); (ii) combined diphtheria, tetanus and pertussis (DTP) vaccine, Haemophilus influenza type B (Hib) and hepatitis B (DTP–Hib–hepatitis B) vaccine; (iii) pneumococcal conjugate vaccine (PCV); (iv) measles vaccine; and (v) yellow fever vaccine. Administrative data were collected on vaccines administered by age group and vaccination coverage surveys were carried out before and after the campaign.FindingsOverall, 294 054 vaccine doses were administered. Vaccination coverage for children aged 6 weeks to 59 months increased to over 85% for the first doses of OPV, DTP–Hib–hepatitis B vaccine and PCV and, in children aged 9 weeks to 59 months, to over 70% for the first measles vaccine dose. In children aged 6 weeks to 23 months, coverage of the second doses of OPV, DTP–Hib–hepatitis B vaccine and PCV was over 58% and coverage of the third doses of OPV and DTP–Hib–hepatitis B vaccine was over 20%. Moreover, 61% (5804/9589) of children aged 12 to 23 months had received two PCV doses and 90% (25933/28764) aged 24 to 59 months had received one dose.ConclusionA preventive, multi-antigen, vaccination campaign was effective in rapidly increasing immunization coverage in a post-conflict setting. To sustain high coverage, routine immunization must be reinforced.

A case of adverse reactions of immune thrombocytopenic purpura caused by poliovirus vaccine

The child patient, male, 4 months and 16 days old, was vaccinated orally by Type I Type III Live Attenuated Oral Poliomyelitis Vaccine (human diploid cells) at 10:45 a.m. on June 1 st of 2016 in Shaoxian Community Health Service Center of our hospital. Two hours after vaccination, the child patient showed erythema scattered on the upper of the left knee, on the right calf and on the abdomen. The forearm of the left upper limb was scattered with punctate rashes. He was admitted to Department of Pediatrics of our hospital at 12:32 on June 1 st of 2016. The diagnosis was “immune thrombocytopenic purpura”. After admission, the child patient received expert consultation and systematic treatment, consequently getting better.

Timeliness of Childhood Primary Immunization and Risk Factors Related with Delays: Evidence from the 2014 Zhejiang Provincial Vaccination Coverage Survey.

Background: this study aimed to assess both immunization coverage and timeliness, as well as reasons for non-vaccination, and identity the risk factors of delayed immunization, for the vaccines scheduled during the first year of life, in Zhejiang province, east China. Methods: A cluster survey among children aged 24–35 months was conducted. Demographic information and socio-economic characteristics of the selected child, the mother, and the household were collected. Immunization data were transcribed from immunization cards. Timeliness was assessed with Kaplan–Meier analysis for each vaccine given before 12 months of age, based on the time frame stipulated by the expanded program on immunization of China. Cox proportional hazard regression was applied to identify risk factors of delayed immunization. Results: A total of 2772 eligible children were surveyed. The age-appropriate coverage ranged from 25.4% (95% CI: 23.7–27.0%) for Bacillus Calmette–Guerin (BCG) to 91.3% (95% CI: 90.2–92.3%) for the first dose of oral poliomyelitis vaccine (OPV1). The most frequent reason for non-vaccination was parent’s fear of adverse events of immunization. Delayed immunizations were associated with mother having a lower education level, mother having a job, delivery at home, increasing number of children per household, and having a lower household income. Conclusions: Although the timeliness of immunization has improved since 2011, necessary steps are still needed to achieve further improvement. Timeliness of immunization should be considered as another important indicator of expanded program on immunization (EPI) performance. Future interventions on vaccination coverage should take into consideration demographic and socio-economic risk factors identified in this study. The importance of adhering to the recommended schedule should be explained to parents.

A safe and reliable neutralization assay based on pseudovirus to measure neutralizing antibody titer against poliovirus.

With the promotion of inactivated poliomyelitis vaccine (IPV) and live attenuated oral poliomyelitis vaccine (OPV), the global reported cases of poliomyelitis have reduced sharply from 0.35 million in 1988 to 74 in 2015. The Polio Eradication & Endgame Strategic Plan published by WHO in 2013 included the strategy of implementation of poliovirus safe handling and containment measures to minimize the risks of facility-associated reintroduction of virus into the polio-free community to prevent the re-import of poliovirus. Toward this strategy, we produced replication-incompetent pseudovirus of poliovirus type 1, 2, 3 attenuated strains by constructing poliovirus capsid expression vectors and poliovirus replicon then transfecting HEK293T cells and developed a pseudovirus-based neutralization assay (pNA) to determine neutralizing antibody titer which is more secure, time-saving and reliable than conventional neutralization assay (cNA). By using anti-poliovirus rat serum, we demonstrated excellent correlation between neutralizing antibody titers measured by cNA and pNA. It was concluded that pNA can be a potential alternative to replace cNA as a safe and time-saving system for titer determination after live poliovirus's safekeeping.

Feasibility of using global system for mobile communication (GSM)-based tracking for vaccinators to improve oral poliomyelitis vaccine campaign coverage in rural Pakistan.

Despite multiple rounds of immunization campaigns, it has not been possible to achieve optimum immunization coverage for poliovirus in Pakistan. Supplementary activities to improve coverage of immunization, such as door-to-door campaigns are constrained by several factors including inaccurate hand-drawn maps and a lack of means to objectively monitor field teams in real time, resulting in suboptimal vaccine coverage during campaigns. Global System for Mobile Communications (GSM) - based tracking of mobile subscriber identity modules (SIMs) of vaccinators provides a low-cost solution to identify missed areas and ensure effective immunization coverage. We conducted a pilot study to investigate the feasibility of using GSM technology to track vaccinators through observing indicators including acceptability, ease of implementation, costs and scalability as well as the likelihood of ownership by District Health Officials. The real-time location of the field teams was displayed on a GSM tracking web dashboard accessible by supervisors and managers for effective monitoring of workforce attendance including 'time in-time out', and discerning if all target areas - specifically remote and high-risk locations - had been reached. Direct access to this information by supervisors eliminated the possibility of data fudging and inaccurate reporting by workers regarding their mobility. The tracking cost per vaccinator was USD 0.26/month. Our study shows that GSM-based tracking is potentially a cost-efficient approach, results in better monitoring and accountability, is scalable and provides the potential for improved geographic coverage of health services.

Communications, Immunization, and Polio Vaccines: Lessons From a Global Perspective on Generating Political Will, Informing Decision-Making and Planning, and Engaging Local Support.

The requirements under objective 2 of the Polio Eradication and Endgame Strategic Plan 2013–2018—to introduce at least 1 dose of inactivated poliomyelitis vaccine (IPV); withdraw oral poliomyelitis vaccine (OPV), starting with the type 2 component; and strengthen routine immunization programs—set an ambitious series of targets for countries. Effective implementation of IPV introduction and the switch from trivalent OPV (containing types 1, 2, and 3 poliovirus) to bivalent OPV (containing types 1 and 3 poliovirus) called for intense global communications and coordination on an unprecedented scale from 2014 to 2016, involving global public health technical agencies and donors, vaccine manufacturers, World Health Organization and United Nations Children’s Fund regional offices, and national governments. At the outset, the new program requirements were perceived as challenging to communicate, difficult to understand, unrealistic in terms of timelines, and potentially infeasible for logistical implementation. In this context, a number of core areas of work for communications were established: (1) generating awareness and political commitment via global communications and advocacy; (2) informing national decision-making, planning, and implementation; and (3) in-country program communications and capacity building, to ensure acceptance of IPV and continued uptake of OPV. Central to the communications function in driving progress for objective 2 was its ability to generate a meaningful policy dialogue about polio vaccines and routine immunization at multiple levels. This included efforts to facilitate stakeholder engagement and ownership, strengthen coordination at all levels, and ensure an iterative process of feedback and learning. This article provides an overview of the global efforts and challenges in successfully implementing the communications activities to support objective 2. Lessons from the achievements by countries and partners will likely be drawn upon when all OPVs are completely withdrawn after polio eradication, but also may offer a useful model for other global health initiatives.

Immunisation status and determinants of left-behind children aged 12-72 months in central China.

Many parents move from rural China to urban areas in search of job opportunities, and leave their children behind to be raised by relatives. We aimed to assess the immunisation coverage, including the 1:3:3:3:1 vaccine series (one dose of Bacilli Chalmette-Guérin vaccine; three doses of live attenuated oral poliomyelitis vaccine; three doses of diphtheria, tetanus and pertussis combined; three doses of hepatitis B vaccine; and one dose of measles-containing vaccine), in children aged 12-72 months and identify the determinants of immunisation uptake among left-behind children in Hubei Province, Central China, in 2014. In this cross-sectional study using the World Health Organization's cluster sampling technique, we surveyed 1368 children from 44 villages in 11 districts of Hubei Province. The socio-demographic and vaccination status data were collected by interviewing primary caregivers using a semi-structured questionnaire and reviewing the immunisation cards of the children. Univariate and multivariate analyses were used to identify the determinants of complete vaccination and age-appropriate vaccination. For each dose of the five vaccines, the vaccination coverage in the left-behind and non-left-behind children was >90%; however, the age-appropriate vaccination coverage for each vaccine was lower in left-behind than in non-left-behind children. For the five vaccines, the fully vaccinated rate of left-behind children were lower than those of non-left-behind children (89·1%, 92·7%; P = 0·013) and age-appropriate immunisation rate of left-behind children were lower than those of non-left-behind children (65·7%, 79·9%; P < 0·001). After controlling for potential confounders, we found that the parenting pattern, annual household income and attitude of the primary caregiver towards vaccination significantly influenced the vaccination status of children. Moreover, we noted a relatively high prevalence of delayed vaccination among left-behind children. Hence, we believe that the age-appropriate immunisation coverage rate among left-behind children in rural areas should be further improved by delivering and sustaining primary care services.

Glutathione is a highly efficient thermostabilizer of poliovirus Sabin strains

Glutathione (GSH) is the most abundant thiol peptide in animal cells and has a critical role in antioxidation. GSH was reported to be essential for stabilization of some enteroviruses, including poliovirus (PV), during viral morphogenesis. Here, we explored the potential use of GSH as a thermostabilizer of oral poliomyelitis vaccine (OPV) formulations. GSH significantly protected the three types of PV from heat-inactivation in a concentration-dependent manner. At a GSH concentration of 20mM, nearly complete protection was observed against heating temperatures up to 53°C for 2min.GSH also markedly protected PV1 from heat-inactivation and this up to 6 h at temperatures of 44°C and 46°C and 3 h at 48°C. The fact that GSH is naturally present at high concentration in the human body makes it an efficient candidate stabilizer for OPV formulations.

A case-control study on the association of pulse oral poliomyelitis vaccination and Gianotti-Crosti syndrome.

Since 1995, the Indian government has been launching two National Immunization Days (NIDs) annually to administer oral polio vaccines (OPVs) to children under the age of 5. Our aim was to investigate the association between OPVs and Gianotti-Crosti syndrome (GCS). A board-certified dermatologist in solo practice conducted the examinations. The patients consulted without the need of a referral. We retrieved files of all children under the age of 5 who were diagnosed with GCS in 18months. There were three NIDs during these months. We charted the number of children 1month before, 1week before, 1week after, and 1month after the three NIDs. A total of 116 children (49 boys and 67 girls) under the age of 5 with GCS were found (average age: 2.9years) within these 18months of three NIDs. Eleven (9.5%) and 105 (90.5%) children developed GCS 1month before and 1month following OPV administration, respectively (RR: 1.81; 95% CI: 1.40-2.35; P<0.0001). Three (2.6%) and 58 (50.0%) children developed GCS 1week before and 1week after OPV administration, respectively (RR: 1.90; 95% CI: 1.12-3.22; P<0.0001). The administration of OPV is significantly associated with the occurrence of GCS in the part of the world that we investigated. As we demonstrated a temporal relationship, this association is likely to be causal.

Exchanges of genomic domains between poliovirus and other cocirculating species C enteroviruses reveal a high degree of plasticity.

The attenuated Sabin strains contained in the oral poliomyelitis vaccine are genetically unstable, and their circulation in poorly immunized populations can lead to the emergence of pathogenic circulating vaccine-derived polioviruses (cVDPVs). The recombinant nature of most cVDPV genomes and the preferential presence of genomic sequences from certain cocirculating non-polio enteroviruses of species C (EV-Cs) raise questions about the permissiveness of genetic exchanges between EV-Cs and the phenotypic impact of such exchanges. We investigated whether functional constraints limited genetic exchanges between Sabin strains and other EV-Cs. We bypassed the natural recombination events by constructing 29 genomes containing a Sabin 2 capsid-encoding sequence and other sequences from Sabin 2 or from non-polio EV-Cs. Most genomes were functional. All recombinant viruses replicated similarly in vitro, but recombination modulated plaque size and temperature sensitivity. All viruses with a 5′UTR from Sabin 2 were attenuated in mice, whereas almost all viruses with a non-polio 5′UTR caused disease. These data highlight the striking conservation of functional compatibility between different genetic domains of cocirculating EV-Cs. This aspect is only one of the requirements for the generation of recombinant cVDPVs in natural conditions, but it may facilitate the generation of viable intertypic recombinants with diverse phenotypic features, including pathogenicity.

Association between timely initiation of hepatitis B vaccine and completion of the hepatitis B vaccine and national immunization program vaccine series

Little is known about the association between the initiation of hepatitis B vaccine (HB vaccine) at birth and completion of the HB vaccine and the national immunization program vaccine (NIPV) series in Fujian, China. A provincial survey, including children in the community and newborns in hospital, was conducted to evaluate coverage with a timely first dose of HB vaccine and the completion of three doses of HB vaccine and the NIPV series in 2013. A proportion of the samples was rechecked to investigate the relationship between the administration of a timely first dose of HB vaccine and completion of the HB vaccine series and the NIPV series (three doses of HB vaccine, one dose of Bacillus Calmette-Guérin vaccine, three doses of oral poliomyelitis vaccine, three doses of diphtheria-tetanus-pertussis vaccine, one dose of measles-containing vaccine, one dose of Japanese encephalitis attenuated live vaccine, and two doses of group A meningococcal polysaccharide vaccine). A total of 6589 subjects (including 3785 community children and 2804 hospital newborns) were included in this study; 97.34% of them received a timely first dose of HB vaccine (≤24h after birth) and 99.10% and 88.27% completed the HB vaccine series and the NIPV series, respectively. Among the 1680 children from eight counties who were rechecked, those with a timely first dose of HB vaccine had higher completion rates of the HB vaccine series and the NIPV series than those with a delayed first dose of HB vaccine (99.69% and 88.90% vs. 83.05% and 79.66%, respectively; both p<0.001). Compared to those with a delayed HB vaccine first dose, the odds ratios for completing the HB vaccine series and the NIPV series among children who received a timely first dose of HB vaccine were 65.96 (95% confidence interval (CI) 21.73-200.25) and 3.24 (95% CI 1.81-5.81), respectively. Coverage with a timely first dose of HB vaccine is high in children in the community and newborns in hospital, and timely receipt of the first dose of HB vaccine is associated with an increased likelihood of completing the HB vaccine series and the NIPV series in Fujian, China.